Proteomic and serological markers for diagnosing cardia gastric cancer and precursor lesions in a Chinese population

Abstract Cardia gastric cancer (CGC) is prevalent in East Asia, and noninvasive, cost-effective screening methods are needed. This study investigated the diagnostic value of serum pepsinogen (PG), gastrin-17 (G-17), Helicobacter pylori (H. pylori) antibodies, and proteomic profiling for CGC and precancerous lesions. We conducted a case-control study involving biopsy-confirmed patients with CGC (n = 60), low-grade intraepithelial neoplasia (CLGD, n = 60), high-grade intraepithelial neoplasia (CHGD, n = 64), and healthy controls (n = 120) matched for age and sex from high-incidence areas in China. Serological markers including PGI, PGII, G-17, and H. pylori were measured using ELISA and Western blot, while plasma protein markers were assessed using Olink® technology. The VSOLassoBag algorithm and nine machine learning (ML) algorithms were employed to identify crucial features and construct predictive models. Various evaluation metrics, including the area under the receiver-operating-characteristic curve (AUC), were utilized to compare predictive performance. Elevated PGII levels, decreased PGR, and H. pylori infection were significantly associated with an increased risk of CGC and precancerous lesions (P for trend